We have been conducting a series of studies designed to measure the effects of using clinical, pharmacologic, and imaging meaures to study antiepileptic drugs. Most recently. we have used both positron emission tomography and magnetic resonance spectroscopy to study the effects of vigabatrin, an experimental antiepileptic drug which blocks degradation of GABA, the main inhibitory neurotransmitter in the brain. Increased GABA levels are thought to lead to seizure reduction. We have found reductions in cerebral glucose metabolism and blood flow associated with increased brain and cerebrospinal fluid GABA levels. These measurements are related to reduced seizure frequency. The wide brain distribution of GABAergic neurons might lead to other effects of drugs like vigabatrin as well. Vigabatrin is anxiolytic in animal models of anxiety, but clinical reports suggest a possible association with depression and psychosis. As part of our blinded trial of vigabatrin, we performed psychiatric rating scales on patients taking placebo or active drug. In the blinded phase, patients who took VGB had lower Zung and Bunney-Hamburg anxiety scores on CBZ+VGB than CBZ alone; there was no change in placebo patients. There was a trend for the BPRS score to decrease with increasing free CSF GABA levels. Seizures decreased significantly on GVG. Improvement on the Zung and Bunney-Hamburg anxiety ratings may be related to increased CSF GABA levels and is consistent with the preclinical anxiolytic profile of VGB, and clinical profiles of other GABAergic medications such as benzodiazepines.